Three-drug H. pylori therapy better for some than four

New results from large Latin American SWOG study contradict clinical trial findings in Europe and Asia; geographic variations in antibiotic resistance may validate different drug regimens for different populations

Aug. 1, 2011

“The ultimate goal is to advance the discussion about whether we should approach stomach cancer prevention by mass eradication programs for H. pylori,” said lead author Dr. E. Robert Greenberg.

Photo Courtesy Dr. E. Robert Greenberg

Helicobacter pylori, the bacterium known to cause peptic ulcers and the primary cause of stomach cancer, may vary geographically, according to new findings. A large clinical trial at seven sites across Latin America has found that a standard three-drug regimen for treating H. pylori is more effective in the population studied than either of two four-drug regimens that proved superior in studies in Europe and Asia.

"This study turns recent literature a bit on its head," said study co-author Dr. William Chey of the University of Michigan. "Virtually all other randomized, controlled trials that have tested the four-drug therapy have found it superior."

But most of that literature reports on research done in Italy and Taiwan, Chey pointed out. The new study, published July 20 in the online edition of The Lancet, suggests H. pylori eradication approaches need to be validated locally rather than relying on findings from studies of other populations. The authors speculate that geographic variations in H. pylori’s resistance to antibiotics might account for part of the discrepancy between populations.

Coordinated by SWOG (formerly known as the Southwest Oncology Group), one of the National Cancer Institute’s cooperative groups, the study took place at both urban and rural sites in Chile, Colombia, Costa Rica, Honduras, Mexico and Nicaragua. The Hutchinson Center is home to SWOG’s statistical center, and several Center researchers contributed to the study, the largest trial of its kind ever conducted.

Researchers randomly assigned 1,463 volunteers infected with H. pylori to one of three treatment regimens. One group took a five-day, four-drug regimen, and a second group took these same four drugs sequentially over a period of ten days. A third group took a standard, 14-day course of two antibiotics plus a proton-pump inhibitor.

Six weeks after starting treatment, each participant was tested for H. pylori infection.

Of those volunteers who took the three-drug, 14-day treatment, 82.2 percent were infection-free. Only 73.6 percent of the group on the five-day regimen and 76.5 percent of those on the ten-day regimen—the same therapies earlier studies had found superior—had overcome their infection.

Stomach cancer prevention: A complicated goal

The trial was part of an initiative exploring ways to reduce the incidence of stomach cancer. According to the International Agency for Research on Cancer, stomach cancer was the fourth most common malignancy and the second leading cause of cancer death in the world in 2008, with an estimated 990,000 new cases and about 738,000 deaths. Approximately 72 percent of new cases occurred in developing countries.

"The ultimate goal is to advance the discussion about whether we should approach stomach cancer prevention by mass eradication programs for H. pylori," said lead author Dr. E. Robert Greenberg, a Center epidemiologist in the Public Health Sciences Division’s SWOG Statistical Center. "There’s lots of thinking that needs to be done and information that needs to be gathered before that decision is made."

Complicating the stomach cancer prevention picture is a small but controversial body of evidence hinting that H. pylori infection may bring benefits as well as harm, reducing rates of childhood asthma and allergies and lowering rates of esophageal cancer, for example.

H. pylori treatment in the U.S.

No large studies comparing the effectiveness of H. pylori treatment regimens have been conducted in the United States, and a pressing question now is which regimen should be recommended to U.S. doctors treating H. pylori.

"Before this trial I thought I knew the answer to that question," Chey said. "Now I’m not so sure."

In addition to Greenberg, Drs. Garnet Anderson, John Crowley and Gary Goodman, all of PHS, contributed to the research.

SWOG is one of the largest cancer clinical trial cooperative groups in the U.S. Funded primarily by the National Cancer Institute, the group designs and conducts clinical trials to improve the practice of medicine in preventing, detecting and treating cancer, and to enhance the quality of life for cancer survivors.